The research proposed is a study of the effects of low doses (sublethal) of ultraviolet (UV) and ionizing radiation on cultured human diploid fibroblasts (HDF). Emphasis is on (1) defining the effects of these radiations on arrested non-mitotic populations of various HDF strains and (2) inducing with these radiations HDF transformants in culture. A fraction of cells from UV-irradiated arrested populations is lost upon subsequent incubation. The extent of cell loss is dose-dependent and cell strain specific. A xeroderma pigmentosum strain is more sensitive to UV than are normal HDF. Experiments proposed are designed to determine a mechanism for cell detachment and death, to define the role of DNA repair, and to define mechanisms of DNA repair in arrested populations. Arrested populations of normal strains are resistant to x-rays. Preliminary results indicate that progeria HDF are sensitive in this assay. Experiments are proposed to define this response and to determine the sensitivity to x-rays of arrested HDF populations of strains classified as x-ray sensitive (ataxia telangiectasia). Experiments to define reasons for the significant difference in response of arrested HDF to UV versus x-rays are also proposed. Attempts to induce HDF transformation using UV and x-rays are proposed. Emphasis is placed on using HDF strains isolated from individuals with predisposition to cancer, using with x-rays and UV chemicals defined as co-carcinogens, and using various culture procedures that may permit expression of a transformation event. The purpose of the proposed research is to define some actions of low doses of both UV and ionizing radiation on cells derived from humans and maintained in culture. The use of arrested, non-dividing populations may represent a model system that more closely approximates the in vivo situation than cultured proliferating populations. Development of procedures for inducing and detecting HDF transformants will define a model system for the study of carcinogenesis.